Journal article
Clinical Activity and Safety of Cabozantinib for Brain Metastases in Patients With Renal Cell Carcinoma
JAMA oncology, Vol.7(12), pp.1815-1823
12/01/2021
DOI: 10.1001/jamaoncol.2021.4544
PMCID: PMC8532040
PMID: 35238907
Abstract
Importance Patients with brain metastases from renal cell carcinoma (RCC) have been underrepresented in clinical trials, and effective systemic therapy is lacking. Cabozantinib shows robust clinical activity in metastatic RCC, but its effect on brain metastases remains unclear.
Objective To assess the clinical activity and toxic effects of cabozantinib to treat brain metastases in patients with metastatic RCC.
Design, Setting, and Participants This retrospective cohort study included patients with metastatic RCC and brain metastases treated in 15 international institutions (US, Belgium, France, and Spain) between January 2014 and October 2020. Cohort A comprised patients with progressing brain metastases without concomitant brain-directed local therapy, and cohort B comprised patients with stable or progressing brain metastases concomitantly treated by brain-directed local therapy.
Exposures Receipt of cabozantinib monotherapy at any line of treatment.
Main Outcomes and Measures Intracranial radiological response rate by modified Response Evaluation Criteria in Solid Tumors, version 1.1, and toxic effects of cabozantinib.
Results Of the 88 patients with brain metastases from RCC included in the study, 33 (38%) were in cohort A and 55 (62%) were in cohort B; the majority of patients were men (n = 69; 78%), and the median age at cabozantinib initiation was 61 years (range, 34-81 years). Median follow-up was 17 months (range, 2-74 months). The intracranial response rate was 55% (95% CI, 36%-73%) and 47% (95% CI, 33%-61%) in cohorts A and B, respectively. In cohort A, the extracranial response rate was 48% (95% CI, 31%-66%), median time to treatment failure was 8.9 months (95% CI, 5.9-12.3 months), and median overall survival was 15 months (95% CI, 9.0-30.0 months). In cohort B, the extracranial response rate was 38% (95% CI, 25%-52%), time to treatment failure was 9.7 months (95% CI, 6.0-13.2 months), and median overall survival was 16 months (95% CI, 12.0-21.9 months). Cabozantinib was well tolerated, with no unexpected toxic effects or neurological adverse events reported. No treatment-related deaths were observed.
Conclusions and Relevance In this cohort study, cabozantinib showed considerable intracranial activity and an acceptable safety profile in patients with RCC and brain metastases. Support of prospective studies evaluating the efficacy of cabozantinib for brain metastases in patients with RCC is critical.
Details
- Title: Subtitle
- Clinical Activity and Safety of Cabozantinib for Brain Metastases in Patients With Renal Cell Carcinoma
- Creators
- Laure Hirsch - Dana-Farber Cancer InstituteNieves Martinez Chanza - Université Libre de BruxellesSubrina Farah - Dana-Farber Cancer InstituteWanling Xie - Dana-Farber Cancer InstituteRonan Flippot - Institut Gustave RoussyDavid A. Braun - Dana-Farber Cancer InstituteNityam Rathi - Huntsman Cancer InstituteJonathan Thouvenin - Institut de Cancérologie StrasbourgKatharine A. Collier - The Ohio State UniversityEmmanuel Seront - Institut Roi Albert II, Department of Medical Oncology, St Luc University Hospital, Brussels, BelgiumGuillermo de Velasco - Medical Oncology Department, University Hospital 12 de Octubre, Madrid, SpainHannah Dzimitrowicz - Duke Medical CenterBenoit Beuselinck - Universitair Ziekenhuis LeuvenWenxin Xu - Dana-Farber Cancer InstituteI. Alex Bowman - The University of Texas Southwestern Medical CenterElaine T. Lam - University of Colorado Cancer CenterBashar Abuqayas - University of IowaMehmet Asim Bilen - Emory UniversityAndreas Varkaris - Beth Israel Deaconess Medical CenterYousef Zakharia - University of IowaMichael R. Harrison - Duke Medical CenterAmir Mortazavi - The Ohio State UniversityPhilippe Barthélémy - Institut de Cancérologie StrasbourgNeeraj Agarwal - Huntsman Cancer InstituteRana R. McKay - University of California San DiegoPriscilla K. Brastianos - Massachusetts General HospitalKatherine M. Krajewski - Brigham and Women's HospitalLaurence Albigès - Institut Gustave RoussyLauren C. Harshman - Dana-Farber Cancer InstituteToni K. Choueiri - Dana-Farber Cancer Institute
- Resource Type
- Journal article
- Publication Details
- JAMA oncology, Vol.7(12), pp.1815-1823
- DOI
- 10.1001/jamaoncol.2021.4544
- PMID
- 35238907
- PMCID
- PMC8532040
- NLM abbreviation
- JAMA Oncol
- ISSN
- 2374-2437
- eISSN
- 2374-2445
- Language
- English
- Date published
- 12/01/2021
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; General Internal Medicine; Internal Medicine
- Record Identifier
- 9984544949602771
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